The long-term objective of this proposal is to develop gene therapy based strategies for the treatment of polycystic kidney disease. During this grant period, an integrated approach focused on gene delivery, expression and therapeutics will be utilized in the Han:SPRD rat model of cystic disease. Specifically, the goals will be: 1) To optimize adenoviral gene delivery and expression to the normal and cystic kidney. Several maneuvers will be tried to further improve in vivo gene transfer efficiency and distribution. 2) To deliver therapeutic genes to the cystic kidney and assess disease progression. These genes encode products with cytotoxic or anti- inflammatory activity. It is hoped that these studies will impact on the therapy of polycystic disease as well as serve as an important first step in building a database on delivering therapeutic genes in vivo to the kidney. As such, applications to a broad range of renal disease can be envisioned. Finally, results obtained, especially in delivery methods and in extending duration of expression, are likely to benefit other areas of gene therapy as well.